Bioengineering can make a significant contribution to the Healthy People 2000 initiative by developing devices for disease prevention and control. This project will combine the efforts of two National Resources, the Wadsworth Center with expertise in imaging nervous system tissues and Cornell University's expertise in nanofabrication. Neural protheses have tremendous potential to restore nervous system functions lost due to physical trauma or disease. Nanofabrication extends this approach to spinal cord and brain implants for stimulating and recording from single or small groups of neurons. The engineering of these devices is well developed; however, their tissue compatibility is a major limitation. In the brain, a "sheath" of cells surrounds the entire implant. Little is known about these cells and the characteristics of this sheath. We will characterize the tissue reaction and determine which cell types contribute to the "sheath". The successful development of long-term implants requires biologically acceptable surfaces providing stable incorporation into brain tissue and low resistance connections with surrounding neurons. This project will study the brain-neural prosthesis interface in order to improve the integration of neural prostheses into brain tissue. Prostheses will be nanofabricated using semiconductor techniques. A three-step procedure will be used to produce prostheses with tissue compatible surfaces. (i) Test surfaces will be modified by physical, chemical, and biochemical methods. Primary cell cultures and automated analysis will allow efficient testing of large numbers of surfaces, analysis of specific populations of cells, e.g. astrocytes, neurons, ependymal cells, etc., and analysis of cell attachment parameters, e.g. adhesion and strength of adhesion. (ii) Organotypic cultures will compare cell-prosthesis interactions in the complex cellular environment of the brain but the absence of movements associated with cardiac output and movement of the brain within the cranium. (iii) Prostheses will be implanted into rat brains to determine if they become integrated into brain tissue or if sheath formation occurs. In addition, biological interfaces between prostheses and brain tissue will be studied by providing prosthetic devices with neuronal or glial components before implantation. Finally, electronic pads will be incorporated into prostheses and conductivity to the adjacent neural tissue will be monitored. These results will indicate if applied voltage produces an additional factor important for tissue compatibility, if tissue compatible prostheses are a stable for long-term stimulation and/or recording of neural networks, and if prostheses will be useful in clinical applications.